Is CAV3 p.Val44Ala (c.131T>C) pathogenic?

CAV3 p.Val44Ala (c.131T>C) is classified Uncertain significance in CAV3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-09). AlphaMissense: likely pathogenic (0.8891); Very rare (popmax 0.00167%, amr); Associated with Cardiovascular phenotype.

What condition is associated with CAV3 p.Val44Ala (c.131T>C)?

CAV3 p.Val44Ala (c.131T>C) is associated with Cardiovascular phenotype, long QT syndrome (ClinVar).

How common is CAV3 p.Val44Ala (c.131T>C) in the general population?

CAV3 p.Val44Ala (c.131T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CAV3 p.Val44Ala (c.131T>C)?

AlphaMissense predicts likely pathogenic (score 0.8891) — an in-silico prediction, not a clinical call.

CAV3 p.Val44Ala

c.131T>C · rs116840788 · VCV864417

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8891 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.8891	likely pathogenic
REVEL	0.92	moderately pathogenic-leaning
SaProt	LLR -11.66	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.7, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 12 kb · p 0.021 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,018 alleles

Overall 0.000137% 2/1,461,844 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,018
European (non-Finnish)	8.47e-05%	1,179,972

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CAV3
Protein: p.Val44Ala
Coding: c.131T>C
MANE Select: NM_033337
dbSNP: rs116840788
Type: single nucleotide variant
Location: chr3:8745542 (GRCh38)
Gene constraint: LOEUF 1.064 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 88.54
Residue 44: a UniProt-annotated variant site (in rmd2)

Full CAV3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: long QT syndrome

Similar variants

CAV3 p.Val44Met Uncertain significance ★★ ⚠ same residue
CAV3 p.Val44= Conflicting classifications of pathogenicity ★ same residue
CAV3 c.114+2T>C Pathogenic ★★ same condition
CAV3 p.Ala46Thr Pathogenic/Likely pathogenic ★★ same condition
CAV3 p.Arg27Gln Pathogenic ★★ same condition
CAV3 p.Trp71Ter Pathogenic/Likely pathogenic ★★ same condition
CAV3 c.114+5G>C Uncertain significance ★★ same condition
CAV3 p.Ala102Val Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cav3-p-val44ala (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown